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This study seeks to understand the neural, cognitive and behavioral effects of low doses of psilocybin administered in the form of dried mushroom material (0.5 g of Psilocybe cubensis) consumed in natural settings following a placebo-controlled double-blind experimental design.
Sub-threshold doses of serotonergic psychedelics are frequently consumed as cognitive enhancers, and due to their purported positive effects on mood, energy and creativity ("microdosing").
The acute and short-term effects of psilocybin (the psychoactive compound of Psilocybe cubensis mushrooms) on several variables will be investigated, comprising spontaneous and evoked electrophysiological brain activity, perception and cognitive function (cognitive flexibility, attention, inhibitory control, conscious access, visual perception), creativity (problem solving, divergent and convergent thinking), behavior (actigraphy and sleep patterns, natural language production) and several domains related to well-being and mental health of the participants.
This study is simultaneously naturalistic (i.e. recruited subjects are intrinsically motivated to microdose, as they have decided to embark in a microdosing protocol) and controlled by expectations, following a double-blind placebo-controlled design. Participants will microdose according to the following schedule:
Two sessions (0.5 g dried Psilocybin mushrooms vs. dried edible mushroom material without psychoactive effects as a placebo condition) will be conducted. A third party will be in charge of generating their active dose and placebo capsules, and they will also implement a blinding procedure.
Each session will span one week of measurements. Subjects will be given a smartwatch to monitor activity and sleeping patterns at the beginning of the week. At days 3 and 5, subjects will take capsules with active mushroom material or placebo, and then several variables will be recorded. Experiments will be conducted in a setting that is natural and comfortable for the participants, e.g. their homes.
The main outcome measures consist of resting state activity recorded with EEG, evoked response potentials and performance during cognitive tasks, behavioral variables obtained with actigraphy and automated sleep scoring, natural language analysis, and several measurs self-reported via standarized questionnaires.
After completion, this study will provide direct evidence concerning the efficacy of microdosing for cognitive enhancement under natural conditions, i.e. those most frequently used by individuals who microdose, as well as provide information concerning the potential underlying neurobiological mechanisms.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Psilocybe cubensis | Active Comparator | 0.5 g dried and powdered P. cubensis in gel capsules, dosing on two separate days, separated by one week from the placebo, randomized order. |
|
| Inactive placebo | Placebo Comparator | Same weight of inactive placebo in gel capsules, dosing on two separate days, separated by one week from the placebo, randomized order. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Psilocybin | Drug | 0.5 g dried Psilocybe cubensis mushroom material, 0.8 mg psilocybin. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Resting state oscillations measured with EEG | Our goal is to study changes in spectral content before and during the acute effects with the purpose of comparing changes with those observed under higher doses of psilocybin. | 1 week |
| Attention | Measured performance in the attentional blink paradigm | 1 week |
| Inhibitory control | Measured using the go/no go experimental paradigm | 1 week |
| Conscious access | Measured using the backward masking paradigm | 1 week |
| Visual perception | Measured using the binocular rivalry paradigm | 1 week |
| Physical activity | Measured using wrist actigraphy using a smartwach | 1 week |
| Divergent thinking | Measured using the Alternative Uses Task (AUT) | 1 week |
| Attention | Measured using the hiearchical mismatch negativity paradigm combined with EEG | 1 week |
| Cognitive flexibility |
| Measure | Description | Time Frame |
|---|---|---|
| Effect positive/negative affect and well-being | Measured using the Positive and Negative Affect Schedule (PANAS) | 1 week |
| Effects on anxiety | Measured using State Trait Anxiety Inventory (STAI) |
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Inclusion Criteria:
Excusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Enzo Tagliazucchi, PhD | National Council of Scientific and Technical Research, Argentina | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Instituto de Fisica de Buenos Aires (IFIBA) | Buenos Aires | 1428 | Argentina |
All raw data will be made available online through a data sharing webside (e.g. Zenodo) upon publication of the pre-pring containing the results of our study.
After publication, indefinite.
Public
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| ID | Term |
|---|---|
| D001519 | Behavior |
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| ID | Term |
|---|---|
| D011562 | Psilocybin |
| ID | Term |
|---|---|
| D026121 | Indole Alkaloids |
| D000470 | Alkaloids |
| D006571 | Heterocyclic Compounds |
| D007211 | Indoles |
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| Placebo | Drug | 0.5 g dried edible non-psychoactive mushroom material. |
|
Measured using the stroop task |
| 1 week |
| Convergent thinking | Measured using the Remote Associations Task (RAT) | 1 week |
| Convergent thinking | Measured using the Wallach-Kogan test (WK) | 1 week |
| 1 week |
| Effects on personality | Measured using the Big Five inventory (BFI) | 1 week |
| Concentration of psilocybin in the dried material | To be measured using high performance liquid chromatography | 1 week |
| D006574 |
| Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D014363 | Tryptamines |
| D054836 | Indolizidines |
| D007212 | Indolizines |